731457

research-article20172017

HICXXX10.1177/2324709617731457Journal of Investigative Medicine High Impact Case ReportsSutton et al

Case Report

Clostridium tertium Peritonitis and Concurrent Bacteremia in a Patient With a History of Alcoholic Cirrhosis

Journal of Investigative Medicine High Impact Case Reports July-September 2017: 1­–4 © 2017 American Federation for Medical Research https://doi.org/10.1177/2324709617731457 DOI: 10.1177/2324709617731457 journals.sagepub.com/home/hic

S. Scott Sutton, PharmD1, Mark Jumper, PharmD1, Ansal Shah, MD1, and Babatunde Edun, MD2

Abstract Spontaneous bacterial peritonitis (SBP) is a recognized cause of morbidity and mortality in cirrhotic patients. Enterobacteriaceae have been isolated from the majority of peritonitis cases and the gram negative aerobe Escherichia coli is the most commonly isolated organism. Anaerobic organisms are rarely isolated because of the high oxygen tension in ascetic fluid. We report a patient with a history of alcoholic cirrhosis who developed SBP and concurrent bacteremia with the anaerobe Clostridium tertium. The patient was successfully treated with intravenous antibiotics and was discharged home on oral ciprofloxacin. This case report is unique in that it is the fourth documented Clostridium tertium SBP case, utilized MALDI-TOF mass spectrometry for organism identification, and susceptibility testing for select antibiotics was performed. Keywords Clostridium tertium, peritonitis, alcoholic cirrhosis

Introduction Primary spontaneous bacterial peritonitis (SBP) is a recognized cause of morbidity and mortality in cirrhotic patients. SBP is an acute bacterial infection of the ascites fluid and is known to affect patients with cirrhosis from any cause, including alcoholic cirrhosis.1,2 The pathophysiology of bacterial introduction in the ascitic fluid is not known; however, cirrhosis predisposes the development of gastrointestinal bacterial overgrowth and increased intestinal permeability.3,4 Enterobacteriaceae have been isolated from the majority of peritonitis cases, and the gram-negative aerobe Escherichia coli is the most commonly isolated organism.3,4 While Enterobacteriaceae are commonly encountered, gram-positive organisms such as streptocococi and enterococci are sometimes found. Anaerobic organisms are rare because of the high oxygen tension in ascetic fluid.3-5 However, there are reports of anaerobic SBP infections. We report the case of a patient with a history of alcoholic cirrhosis who developed SBP and concurrent bacteremia with the anaerobe Clostridium tertium.

hernia surgery approximately 2 months prior to current admission. Temperature on admission was 102.2°F, otherwise his vitals were stable with no signs of sepsis or hemodynamic instability. Abdominal exam revealed diffuse tenderness and positive fluid thrill. His only subjective complaint was pain. Laboratory findings on admission are listed in Table 1, with abnormalities including serum white blood cell count and albumin. The patient’s cirrhosis severity was rated as a ChildPugh Class B. Initial paracentesis fluid study results are listed in Table 2. The patient’s urinalysis was negative and nondiagnostic. Empiric antibiotic therapy was initiated with intravenous (IV) cefotaxime. The antibiotics were subsequently changed to IV vancomycin and meropenem due to persistent fever and abdominal pain. A repeat ultrasound-guided paracentesis was conducted on day 4 of admission, with 2 liters of fluid removed. Ascitic fluid cultures grew out anaerobic grampositive rods. On day 5, the organism was identified as C tertium by matrix-assisted laser desorption/ionization-time of 1

Case Report A 60-year-old man was admitted with worsening abdominal pain, nausea, vomiting, fever, and grossly extended abdomen accompanied by 1+ bilateral lower extremity edema. His symptoms had been ongoing for 1 week. Contributory medical history was significant for alcoholic cirrhosis and umbilical

University of South Carolina, Columbia, SC, USA Dorn VA Medical Center, Columbia, SC, USA

2

Received July 25, 2017. Revised August 8, 2017. Accepted August 11, 2017. Corresponding Author: Scott Sutton, University of South Carolina, 715 Sumter Street, Columbia, SC 29201, USA. Email: [email protected]

Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

2

Journal of Investigative Medicine High Impact Case Reports

Table 1.  Laboratory Results Upon Admission. Parameters

Readings

Normal Ranges

15.2 13.9 196 137  3.5 22  1.1  9.0  2.7  5.6 105 44 74  1.4

3.6-11.1 K/mm3 12.9-16.1 g/dL 165-353 K/mm3 135-145 mmol/L 3.5-5.1 mmol/L 7-26 mg/dL 0.5-1.3 mg/dL 8.4-10.2 mg/dL 3.5-5.0 g/dL 0.2-1.2 mg/dL 40-150 U/L 0-55 U/L 5-34 U/L 0.8-1.2

White cell count Hemoglobin Platelet Sodium Potassium Blood urea nitrogen Creatinine Calcium Albumin Total bilirubin Alkaline phosphatase Alanine aminotransferase Aspartate aminotransferase International normalized ratio

Table 2.  Paracentesis Fluid Studies. Parameters Total cells Nucleated cells Polymorphonuclear leukocytes Absolute polymorphonuclear leukocytes Lymphocytes Red blood cells Total protein

Readings 23 777 cells/mm3 15 707 cells/mm3 84% 13 193 cells/mm3 9% 8064 cells/mm3 1.6 g/dL

flight (MALDI-TOF) mass spectrometry. Following isolation of the anaerobic organism, ciprofloxacin and metronidazole were added to the vancomycin pending susceptibility testing and meropenem was discontinued. Over the next 24 hours, the patient improved clinically, with defervescence and leukocytosis resolution. Repeat cultures on day 7 were negative. Susceptibility testing was conducted using E-test, which showed that the C tertium was sensitive to vancomycin, ciprofloxacin, trimethoprim/sulfamethoxazole, meropenem, and clindamycin. IV antibiotics were continued until repeat cultures were finalized as negative, and the patient was discharged on oral ciprofloxacin.

Discussion Clostridium tertium is a ubiquitous gram-positive bacillus isolated in soil and the gastrointestinal tract. C tertium distinguishes itself among the clostridia as a non–toxin-producing, aerotolerant species.5 Typically, C tertium does not have pathogenic potential, and its role as a human pathogen is uncertain.6,7 Infection with the organism has been rare after initial description in 1917. However, C tertium has documented cases of SBP, intraabdominal infection, enterocolitis, meningitis, septic arthritis, pneumonia, and necrotizing fasciitis.5-13 Case reports have identified neutropenia, mucosal injury, β-lactam antibiotics

Figure 1.  Gram stain of Clostridium tertium, which is an anaerobic, motile, gram-positive bacterium. It is easily decolorized in gram-stained smears and can be mistaken for a gram-negative organism.

(third-generation cephalosporins), cytotoxic chemotherapy, and severe liver disease as predisposing factors for C tertium infection.5 While scare, case reports document that C tertium is a cause of SBP. Our case report of a patient with alcoholic cirrhosis adds to the literature regarding C tertium SBP. Previously published case reports include the following: •• Butler and Pitt reported a case of C tertium SBP in a 42-year-old female with a history of cirrhosis.8 The patient was admitted for management of hepatic encephalopathy with subsequent development of peritonitis. Clinical and microbiological cure was achieved with the cephamycin antibiotic cefoxitin. •• Miller et al reported 32 cases of C tertium bacteremia over a 7-year span.5 All 32 patients presented with fever, 59% had one or more abdominal symptoms, 9 had diarrhea (including 5 with a positive test for Clostridium difficile toxin), 9 had abdominal pain, 5 had nausea, and 1 had constipation. Twenty-nine of the 32 cases involved neutropenic patients, all of which were status post chemotherapy within 9 to 21

Sutton et al

3

Figure 2.  E-test of select antibiotics tested against Clostridium tertium. E-testing was performed to evaluate the susceptibility of C tertium to select antibiotics. The organism was susceptible to vancomycin, ciprofloxacin, sulfamethoxazole/trimethoprim, meropenem, and clindamycin.

days before the onset of C tertium bacteremia. The 3 nonneutropenic patients had underlying host factors disposing them to C tertium infection: (1) chronic alcoholism and end-stage liver disease, (2) systemic lupus erythematosus receiving high-dose corticosteroids and recent placement of a percutaneous gastrostomy tube, and (3) Crohn’s disease. Four patients died within 1 week after the isolation of C tertium, including the patient with SBP. The patient with SBP was a 43-year-old patient with end-stage liver disease with concurrent bacteremia. •• Victor and Opal reported 43 patients with SBP during a 5-year period.10 Alcoholic liver disease was the underlying cause in 72% of the cases, and Enterobacteriaceae accounted for 66% of the cases. There were 2 cases of anaerobic infections (one patient had C tertium SBP with concurrent bacteremia). The overall mortality rate was 65% (mortality rates were not discussed regarding individual cases). These case reports demonstrate that C tertium is a rare cause of SBP. However, C tertium is often mistaken for Bacillus or Lactobacillus species because of its micromorphology and growth pattern (Figure 1), which could lead to underdiagnoses.14-16 Therefore, thorough identification of this species is critical. Unfortunately, traditional identification of anaerobes is time-consuming and cumbersome. New methods based on mass spectrometry such as MALDI-TOF mass spectrometry, which have been developed for the rapid identification of

bacterial strains, can offer new possibilities for identification.15,16 Our case report is unique as we identified C tertium by MALDI-TOF. The appropriate identification of the organism allowed for early identification and susceptibility tests to be ordered. Ultimately, the bacterial identification allowed for targeted antibiotic therapy. Targeted therapy is critical for C tertium because in contrast to other clostridial species, treatment can be a challenge.5,15,16 Although studies evaluating sufficient numbers of strains are lacking, C tertium exhibits resistance to various antibiotics including third- and fourth-generation cephalosporins. Additionally, our article is unique in that we performed e-testing to evaluate the susceptibility of C tertium to select antibiotics. The organism was susceptible to vancomycin, ciprofloxacin, sulfamethoxazole/ trimethoprim, meropenem, and clindamycin (Figure 2). Clostridium tertium’s sporadic presence as an infectious pathogen in SBP can make treatment decisions difficult and lead to inappropriate antibiotics. Four characteristics of C tertium make it a clinically important bacterium worthy of consideration in evaluating SBP patients: (1) antibiotic resistance, (2) aerotolerant nature and difficulty in identification, (3) human commensal, and (4) potential to cause mortality. C tertium exhibits resistance to several antibiotics including antibiotics recommended for empiric therapy for SBP.5 C tertium is often resistant to clindamycin, metronidazole, and cephalosporins; however, the C tertium identified in our case report was susceptible to clindamycin. For SBP patients empirically treated with guideline-recommended antibiotics, clinical monitoring is highly recommended to suspect

4 alternative etiologic organisms.17 In our patient, antibiotics were selected based on expected etiology (eg, Escherichia coli); however, once our patient did not respond clinically, antibiotics were adjusted. Second, C tertium is aerotolerant, allowing the bacterium to survive the oxygen-rich environment of the ascitic fluid.5,10 It also provides C tertium the ability to grow morphologically distinct features under aerobic versus anaerobic conditions.15,16 When cultured under aerobic conditions, C tertium was initially identified as a Lactobacillus species in a case report, and only under careful anaerobic conditions was the proper bacterium identified.14 This oftentimes leads to false identification and delay in proper antibiotic treatment. The introduction of MALDITOF for the rapid identification of bacterial pathogens may be particularly helpful in this group of organisms. Third is C tertium’s presence as a normal commensal of the gastrointestinal tract. This, coupled with gastrointestinal abnormalities or immunosuppression, may set the stage for potential overgrowth and infection.5 Finally, C tertium is associated with mortality. Of the 4 case reports currently existing of C tertium SBP, one patient had died, two responded to therapy, and one is unknown. C tertium causing other types of infections has also demonstrated a mortality potential. While the majority of C tertium cases are associated with patients with neutropenia, there are cases demonstrating that C tertium is an important cause in a non-neutropenic patient.5,8,10,13

Conclusion This is a unique case of C tertium SBP and bacteremia in a patient with alcoholic cirrhosis. The patient was successfully treated with intravenous antibiotics and was discharged home on oral ciprofloxacin. The goal of this case report is to draw attention to the infectious potential of C tertium. Additionally, this case report is unique in that it is the fourth documented C tertium SBP case, utilized MALDI-TOF for identification, and susceptibility testing for select antibiotics was performed. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics Approval Our institution does not require ethical approval for reporting individual cases or case series.

Informed Consent Informed consent for patient information to be published in this article was not obtained because our institution does not require it for the type of data published.

Journal of Investigative Medicine High Impact Case Reports References 1. Wiest R, Krag A, Gerbes A. Spontaneous bacterial peritonitis: recent guidelines and beyond. Gut. 2012;61:297-310. 2. Singh N, Wagener MM, Gayowski T. Changing epidemiology and predictors of mortality in patients with spontaneous bacterial peritonitis at a liver transplant unit. Clin Microbiol Infect. 2003;9:531-537. 3. González Alonso R, González García M, Albillos Martínez A. Physiopathology of bacterial translocation and spontaneous bacterial peritonitis in cirrhosis [in Spanish]. Gastroenterol Hepatol. 2007;30(2):78-84. 4. Barshak M, Kasper DL. Intraabdominal infections and abscesses. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill; 2015. 5. Miller DL, Brazer S, Murdoch D, Reller LB, Corey GR. Significance of Clostridium tertium bacteremia in neutropenic and nonneutropenic patients: review of 32 cases. Clin Infect Dis. 2001;32:975-978. 6. Salvador F, Porte L, Durán L, et al. Breakthrough bacteremia due to Clostridium tertium in a patient with neutropenic fever, and identification by MALDI-TOF mass spectrometry. Int J Infect Dis. 2013;17:e1062-e1063. 7. Vanderhofstadt M, André M, Lonchay C, et al. Clostridium tertium bacteremia: contamination or true pathogen? A report of two cases and a review of the literature. Int J Infect Dis. 2010;14(Suppl 3):e335-e337. 8. Butler T, Pitt S. Spontaneous bacterial peritonitis due to Clostridium tertium. Gastroenterology. 1982;82:133-134. 9. King BM, Ranck BA, Daugherty FD, Rau CA. Clostridium tertium septicemia. N Engl J Med. 1963;269:467-469. 10. Victor GH, Opal SM. Spontaneous bacterial peritonitis: analysis of treatment and outcome. Can J Infect Dis. 1991;2(4): 147-154. 11. Ingram CW, Cooper JN. Clostridial bloodstream infections. South Med J. 1989;82:29-31. 12. Ray P, Das A, Singh K, Bhansali A, Yadav TD. Clostridium tertium in necrotizing fasciitis and gangrene. Emerg Infect Dis. 2003;9:1347-1348. 13. Chalhoub V, Kallab R, El Hajj A, Hachem K, Yazbeck P. Septic shock due to Clostridium tertium in an immunocompetent patient following colitis without inflammatory bowel disease. Anaesth Crit Care Pain Med. 2016;35:167-168. 14. You MJ, Shin GW, Lee CS. Clostridium tertium bacteremia in a patient with glyphosate ingestion. Am J Case Rep. 2015;16: 4-7. 15. Grosse-Herrenthey A, Maier T, Gessler F, et al. Challenging the problem of clostridial identification with matrix-assisted laser desorption and ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Anaerobe. 2008;14:242-249. 16. Nagy E, Becker S, Kostrzewa M, Barta N, Urbán E. The value of MALDI-TOF MS for the identification of clinically relevant anaerobic bacteria in routine laboratories. J Med Microbiol. 2012;61:1393-1400. 17. Runyon BA. Management of adult patients with ascites due to cirrhosis: update 2p12. http://www.aasld.org/sites/ default/files/guideline_documents/141020_Guideline_ Ascites_4UFb_2015.pdf. Accessed July 10, 2017.

Clostridium tertium Peritonitis and Concurrent Bacteremia in a Patient With a History of Alcoholic Cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a recognized cause of morbidity and mortality in cirrhotic patients. Enterobacteriaceae have been isolated ...
445KB Sizes 0 Downloads 11 Views